Predictive ability of novel volumetric and geometric indices derived from dual-energy X-ray absorptiometric images of the proximal femur for hip fracture compared with conventional areal bone mineral density: the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

Areal BMD (aBMD) from DXA is not a sufficiently accurate predictor of fracture. Novel volumetric BMD derived from 3D modeling of the hip from DXA images significantly improved the predictive ability for hip fracture relative to aBMD at the femoral neck, but not aBMD at the total hip. INTRODUCTION: To clarify whether volumetric and geometric indices derived from novel three-dimensional (3D) modeling of the hip using dual-energy X-ray absorptiometric (DXA) images improve hip fracture prediction relative to areal bone mineral density (aBMD). METHODS: We examined 1331 women who had completed the baseline survey and at least one follow-up survey over 20 years (age 40-79 years at baseline). Each survey included aBMD measurement at the hip by DXA. Volumetric and geometric indices of the hip at baseline and the 10-year follow-up were estimated from DXA images using a 3D modeling algorithm. Incident hip fractures during the 20-year follow-up period were identified through self-report. Cox proportional hazards regression models allowing for repeated measurements of predictors and outcomes were constructed, and their predictive ability for hip fracture was evaluated using areas under receiver operating characteristic curves (AUCs) and net reclassification improvement (NRI) over aBMD at the femoral neck (FN) and total hip (TH) as references. RESULTS: During a median follow-up of 19.8 years, 68 incident hip fractures were identified (2.22/1000 person-years). A significantly larger AUC of trabecular volumetric BMD (vBMD) at the total hip (AUC = 0.741), femoral neck (AUC = 0.748), and intertrochanter (AUC = 0.738) and significant NRI (0.177, 0.149, and 0.195, respectively) were observed compared with FN-aBMD (AUC = 0.701), but not TH-aBMD. CONCLUSIONS: vBMD obtained from 3D modeling using routinely obtained hip DXA images significantly improved hip fracture risk prediction over conventional FN-aBMD, but not TH-aBMD. TRIAL REGISTRATION: The Japanese Population-Based Osteoporosis (JPOS) Cohort Study was retrospectively registered as UMIN000032869 in the UMIN Clinical Trials Registry on July 1, 2018.

Total 25-hydroxyvitamin D levels predict fracture risk: results from the 15-year follow-up of the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

We found that community-dwelling women with 25-hydroxyvitamin D levels <20 ng/mL compared to levels ≥20 ng/mL indicated increased risks for clinical, non-vertebral, and fragility fractures during 5 years. Furthermore, the increased risks of non-vertebral fractures remained significant in 10 and 15 years after adjusting for age and bone mineral density. INTRODUCTION: We examined whether total 25-hydroxyvitamin D (25[OH]D) levels are associated with fracture risk over 15 years in a Japanese female cohort. METHODS: Of 1437 community-dwelling women aged ≥50 years in the baseline survey, 1236 provided information regarding fractures during a 15-year follow-up period. The analysis included 1211 women without early menopause or diseases affecting bone metabolism. RESULTS: Over 15 years, 269 clinical (224 non-vertebral, 149 fragility) fracture events were confirmed. Incidence rates categorized by 25(OH)D levels (<10, 10-20, 20-30, and ≥30 ng/mL) indicated a significant divergence for any clinical fractures in 5 years (log rank test p = 0.016) and for non-vertebral fractures in 5, 10, and 15 years (p < 0.001, p = 0.001, p = 0.017, respectively). Hazard ratios (HRs) for 25(OH)D levels <10 and 10-20 ng/mL compared to levels ≥30 ng/mL during 5 years indicated significances for clinical fractures (HR 4.93 with p = 0.009, HR 3.00 with p = 0.034) and for non-vertebral fractures (HR 6.55 with p = 0.005, HR 3.49 with p = 0.036). Those with levels <20 ng/mL compared to those with levels ≥20 ng/mL indicated significant increased risks for clinical fractures (HR 1.72 with p = 0.010), non-vertebral fractures (HR 2.45 with p < 0.001), and fragility fractures (HR 2.00 with p = 0.032) in 5 years. The HR of non-vertebral fractures for levels <20 ng/mL remained significant during 15 years (HR 1.42 with p = 0.012) after adjustment for age and femoral neck bone mineral density. CONCLUSIONS: Low 25(OH)D levels, especially <20 ng/mL, were associated with elevated fracture risks in Japanese women.

Incident fracture associated with increased risk of mortality even after adjusting for frailty status in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

Frail elderly individuals have elevated risks of both fracture and mortality. We found that incident fractures were associated with an increased risk of death even after adjusting for pre-fracture frailty status as represented by physical performance tests and laboratory tests for common geriatric diseases in community-dwelling elderly Japanese men. INTRODUCTION: While fractures reportedly increase the risk of mortality, frailty may complicate this association, generating a false-positive result. We evaluated this association after adjusting for pre-fracture levels of frailty. METHODS: We examined 1998 community-dwelling ambulatory men aged ≥65 years at baseline in the Fujiwara-kyo Osteoporosis Risk in Men Study for frailty status as represented by activities of daily living (ADL), physical performance tests (grip strength, one-foot standing balance with eyes open, timed 10-m walk), and laboratory sera tests. Participants were then followed for 5 years for incident clinical fractures and death. Effects of incident fracture on death were determined by Cox proportional hazards model with the first fracture during follow-up as a time-dependent predictor and with frailty status indices as covariates. RESULTS: We identified 111 fractures in 99 men and 138 deaths during the follow-up period (median follow-up, 4.5 years). Participants with incident fractures did not have significantly worse frailty statuses, but did show a significantly higher cumulative mortality rate than those without fractures (p = 0.0047). Age-adjusted hazard ratio (HR) of death for incident fracture was 3.57 (95 % confidence interval: 2.05, 6.24). When adjusted for physical performance, this decreased to 2.77 (1.51, 5.06), but remained significant. The HR showed no significant change when adjusted for laboratory test results (3.96 (2.26, 6.94)). Exclusion of deaths within the first 24 months of follow-up did not alter these results. CONCLUSION: Incident clinical fracture was associated with an elevated risk of death independently of pre-fracture levels of frailty in community-dwelling elderly men.

Association between Dairy Product intake and Risk of Osteoporotic Fractures in Postmenopausal Japanese Women: Secondary Analysis of 15-Year Follow-Up data from the Japanese Population-Based Osteoporosis (JPOS) Cohort Study.

OBJECTIVES: Few prospective cohort studies have evaluated the relationship between dairy product intake frequency and risk of osteoporotic fractures in Asians. This study aimed to investigate the association between habitual dairy product intake and risk of osteoporotic fractures. DESIGN: Secondary analysis of prospective cohort study. SETTING: Five municipalities of Japan. PARTICIPANTS: This study included 1,429 postmenopausal Japanese women (age ≥45 years at baseline). MEASUREMENTS: Baseline milk-intake frequency was obtained using nurse-administered questionnaires. Intakes of yogurt and cheese, and estimated calcium intake, were assessed using a validated food frequency questionnaire. Osteoporotic fracture was defined as a clinical fracture diagnosed using radiography. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Over a median follow-up period of 15.1 years (interquartile range [IQR], 10.1-15.4 years; total, 18,118 person-years), 172 women sustained at least one osteoporotic fracture. The proportions of participants with milk intakes <1, 1, and ≥2 cups/d were 34.4%, 48.0%, and 17.6%, respectively. After adjustment for age, frequency of yogurt intake, frequency of cheese intake, body mass index, history of osteoporotic fractures, and frequency of natto intake, the HRs compared with that for milk intake <1 cup/d were 0.71 (95% CI: 0.51-0.98) and 0.57 (95% CI: 0.35-0.92) for 1 cup/d and ≥2 cups/d, respectively. After adjustment for bone mineral density, HR significance for milk intakes ≥2 cups/d remained significant. Yogurt and cheese intakes were not related to the risk of osteoporotic fractures. CONCLUSION: High habitual milk intake, but not a habitual yogurt or cheese intake is associated with a decreased risk of osteoporotic fractures, independent of bone mineral density, in postmenopausal Japanese women.

Fracture risk prediction using FRAX®: a 10-year follow-up survey of the Japanese Population-Based Osteoporosis (JPOS) Cohort Study.

UNLABELLED: We evaluated the predictive ability of FRAX® in a cohort of 815 Japanese women. The observed 10-year fracture rate did not differ significantly from that predicted by FRAX®. The predictive ability of FRAX® without femoral neck bone mineral density (BMD) was similar to that with femoral neck BMD. INTRODUCTION: We evaluated the ability of the Japanese version of FRAX®, a World Health Organization fracture risk assessment tool, to predict the 10-year probability of osteoporotic fracture. METHODS: Self-reported major osteoporotic fracture (N = 43) and hip fracture (N = 4) events were ascertained in the 10-year follow-up survey of the Japanese Population-Based Osteoporosis Cohort Study. Participants were 815 women aged 40-74 years at the baseline survey. Receiver operating characteristic curve analysis compared FRAX® with multiple logistic models based on age, body weight, and femoral neck BMD. RESULTS: The number of observed major osteoporotic or hip fracture events did not differ significantly from the number of events predicted by the FRAX® model (with or without BMD). The area under the curve (AUC) value for FRAX® with BMD for predicting major osteoporotic fractures was similar to that of a logistic model with age, body weight, and BMD (0.69 vs. 0.71, respectively; p = 0.198); the AUC of FRAX® with BMD for predicting hip fractures was similar to that of a model based on age and BMD (0.88 vs. 0.89, respectively; p = 0.164). The AUCs of FRAX® without BMD for predicting major osteoporotic and hip fractures were similar to those with BMD (0.69 vs. 0.67, respectively; p = 0.121; 0.88 vs. 0.86, respectively; p = 0.445). CONCLUSIONS: The Japanese version of FRAX® without BMD estimated the 10-year probability of osteoporotic fracture in this population with few clinical risk factors as similar to that of FRAX® with BMD.

Peroxisome proliferator-activated receptor gamma polymorphism is related to peak bone mass: the JPOS study.

UNLABELLED: We analyzed 1,217 women to examine the effect of peroxisome proliferator-activated receptors gamma (PPARgamma) C161 --> T on bone status. Among 664 premenopausal women, the C161 --> T is associated with low bone mineral density (BMD) at the total hip and femoral neck. Moreover, the odds ratio for osteopenia or osteoporosis at the femoral neck was 1.98 for premenopausal CT/TT genotypes. INTRODUCTION: The impact of PPARgamma on BMD has not been conclusively established. We examined if PPARgamma C161T polymorphism is associated with BMD and its change. METHODS: We conducted a baseline survey in 1996 and a 10-year follow-up survey, Japanese Population-based Osteoporosis Study, with a sample population representative of Japanese women. Of these, 1,217 participants in the 1996 survey were analyzed cross-sectionally, while longitudinal analysis was performed on 563 women. A P value < 0.0042 (=0.05/12 for three menstrual statuses and four skeletal sites) was considered statistically significant after Bonferroni correction in multiple testing for cross-sectional analysis. RESULTS: The total hip and femoral neck BMDs were significantly higher for CC genotype than for CT/TT genotypes among 664 premenopausal women (P = 0.0020, P = 0.0022, respectively). Compared to the CC genotype, the odds ratio for osteopenia or osteoporosis (T-scores below -1) at the femoral neck was 1.98 for premenopausal CT/TT genotypes with statistical significance (P = 0.0041). Change of BMD at either skeletal site during the follow-up period was not significantly different for either menstrual status. CONCLUSIONS: We conclude that the PPARgamma C161T is associated with low peak bone mass.

Prevalent vertebral deformity independently increases incident vertebral fracture risk in middle-aged and elderly Japanese women: the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

SUMMARY: Prevalent vertebral deformity increases incident vertebral fracture risk according to studies focusing primarily on Caucasian elderly populations. We report a 3-fold increase in this risk in a population-based cohort of Japanese women after adjusting for subject propensity for having vertebral deformities. This relationship tended to be stronger in middle-aged women. INTRODUCTION: Evidence on increased risk of incident vertebral fractures associated with vertebral deformity in middle-aged women is limited. We aimed to evaluate this risk in a population-based cohort of Japanese women. METHODS: We followed 712 women aged 50-79 years at baseline randomly selected from 3 municipalities in Japan for 6 years. McCloskey-Kanis criteria identified vertebral deformities on X-ray absorptiometric images. At follow-up, vertebra with > or = 20% height reduction from baseline were considered incident fractures. Rate ratio (RR) of incident fracture for prevalent vertebral deformities was calculated using the Poisson regression equation adjusted for propensity of having vertebral deformities based on potential risk factors. RESULT: Vertebral fractures occurred in 73 women (10.3%). Crude RR of vertebral deformity-associated fracture was 4.63 [95% confidence interval (CI), 3.04-7.04] and decreased to 2.96 (95% CI, 1.77-4.94) after propensity score adjustment. Adjusted RR was generally greater in younger women at 7.19 (95% CI, 1.04-49.6), 3.19 (95% CI, 1.27-7.97), and 2.34 (95% CI, 1.33-4.11) for women aged 50-59, 60-69, and 70-79 years, respectively (p = 0.0527 for those aged 50-59 vs 70-79). CONCLUSION: Vertebral deformity was associated with a 3-fold increase in subsequent vertebral fracture risk in Japanese women, and this association was stronger in middle-aged women.

Low bone mass is associated with carotid atherosclerosis in postmenopausal women: the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

UNLABELLED: We analyzed 609 women belonging to the JPOS study in a 10-year follow-up survey, to examine the association of osteoporosis with atherosclerosis. Osteoporosis or prevalent vertebral fracture at baseline was associated with increased intima-media thickness of the carotid bifurcation in postmenopausal women, adjusted for age, BMI, and other variables at baseline. INTRODUCTION: Whether low bone mass predicts increased carotid atherosclerosis has not been fully investigated. METHODS: In 2006, we conducted a 10-year follow-up survey of 1,040 women (follow-up rate: 68.6%). We analyzed 609 women > or =50 years old in 2006 without a history of cardiovascular or connective tissue diseases at baseline. BMD and evaluation of vertebral fracture at baseline were used. The intima-media thickness of carotid bifurcation (BIF-IMT) was measured by B-mode ultrasonography in 2006. RESULTS: Adjusted BIF-IMT values of subjects with spine T-score > or =-1, between-2.5 and -1, and <-2.5 or prevalent vertebral fracture were 1.19 mm, 1.34 mm, 1.57 mm, respectively, in women with less than 10 years since menopause (YSM) (n = 159), 1.30 mm, 1.32 mm, 1.53 mm, in women with YSM > or =10 without a history of hypertension at baseline (n = 144) (both with p < 0.05 for linear trend). Those values among no versus prevalent vertebral fracture in women with YSM > or =10 were 1.40 mm, 1.66 mm with p < 0.05 (n = 202). Those associations were independent of age, BMI, total cholesterol, smoking and drinking habits, history of diabetes mellitus, and hypertension (for women with YSM < 10) at baseline. CONCLUSION: Osteoporosis including prevalent vertebral fracture may be associated with carotid atherosclerosis in the first 10 years of postmenopausal women.

Isolation and characterization of Xenopus laevis aldolase B cDNA and expression patterns of aldolase A, B and C genes in adult tissues, oocytes and embryos of Xenopus laevis.

Following previous cloning and expression studies of Xenopus aldolase C (brain-type) and A (muscle-type) cDNAs, we cloned here two Xenopus aldolase B (liver-type) cDNAs (XALDB1 and XALDB2, 2447 and 1490 bp, respectively) using two different liver libraries. These cDNAs had very similar ORF with only one conservative amino acid substitution, but 3'-UTR of XALDB1 contained ca. 1 kb of unrelated reiterated sequence probably ligated during library construction as shown by genomic Southern blot analysis. In adult, aldolase B mRNA (ca. 1.8 kb) was expressed strongly in kidney, liver, stomach, intestine, moderately strongly in skin, and very weakly in all the other tissues including muscles and brain, which strongly express aldolase A and C mRNAs, respectively. In oocytes and early embryos, aldolase A and C mRNAs occurred abundantly as maternal mRNAs, but aldolase B mRNA occurred only at a residual level, and its strong expression started only after the late neurula stage, mainly in liver rudiment, pronephros, epidermis and proctodeum. Thus, active expression of the gene for aldolase B, involved in dietary fructose metabolism, starts only later during development (but before the feeding stage), albeit genes for aldolases A and C, involved in glycolysis, are expressed abundantly from early stages of embryogenesis, during which embryos develop depending on yolk as the only energy source.

Quantitative expression studies of aldolase A, B and C genes in developing embryos and adult tissues of Xenopus laevis.

We previously cloned cDNAs for all the members (A, B and C) of Xenopus aldolase gene family, and using in vitro transcribed RNAs as references, performed quantitative studies of the expression of three aldolase mRNAs in embryos and adult tissues. A Xenopus egg contains ca. 60 pg aldolase A mRNA and ca. 45 pg aldolase C mRNA, but contains only ca. 1.5 pg aldolase B mRNA. The percent composition of three aldolase mRNAs (A:B:C) changes from 56:1.5:42.5 (fertilized egg) to 54:10:36 (gastrula), to 71:14.5:14.5 (neurula) and to 73:20:7 (tadpole) during development. These results are compatible with the previous results of zymogram analysis that aldolases A and C are the major aldolases in early embryos, whose development proceeds depending on yolk as the only energy source. Aldolase B mRNA is expressed only late in development in tissues such as pronephros, liver rudiment and proctodeum which are necessary for the future dietary fructose metabolism, and the expression pattern is consistent to that in adult tissues. We also show that three aldolase genes are localized on different chromosomes as single copy genes.

Overexpression of S-adenosylmethionine decarboxylase (SAMDC) activates the maternal program of apoptosis shortly after MBT in Xenopus embryos.

Overexpression of S-adenosylmethionine decarboxylase (SAMDC) mRNA in 1- and 2-cell stage Xenopus embryos induces cell autonomous dissociation at the late blastula stage and developmental arrest at the early gastrula stage. The induction of cell dissociation took place "punctually" at the late blastula stage in the SAMDC-overexpressing cells, irrespective of the stage of the microinjection of SAMDC mRNA. When we examined the cells undergoing the dissociation, we found that they were TUNEL-positive and contained fragmented nuclei with condensed chromatin and fragmented DNA. Furthermore, by injecting Xenopus Bcl-2 mRNA together with SAMDC mRNA, we showed that SAMDC-overexpressing embryos are rescued completely by Bcl-2 and becometadpoles. These results indicatethat cell dissociation induced by SAMDC overexpression is due to apoptotic cell death. Since the level of S-adenosylmethionine (SAM) is greatly reduced in SAMDC-overexpressing embryos and this induces inhibition of protein synthesis accompanied by the inhibition of DNA and RNA syntheses, we conclude that deficiency in SAM induced by SAMDC overexpression activates the maternal program of apoptosis in Xenopus embryos at the late blastula stage, but not before. We propose that this mechanism serves as a surveillance mechanism to check and eliminate cells physiologically damaged during the cleavage stage.

A novel polymorphism in the promoter region for the human osteocalcin gene: the possibility of a correlation with bone mineral density in postmenopausal Japanese women.

We present a polymorphism of the human osteocalcin gene (also known as BGP, for bone Gla protein) due to a 1 base pair (bp) substitution from cytosine to thymine at position 298 nucleotides (nt), which is at position 198 nt upstream from the BGP exon 1. This mutation was detected by single-strand conformation polymorphism analysis after polymerase chain reaction for the osteocalcin gene fragment (326 bp) and sequencing analysis. The cytosine/thymine polymorphism can be defined by restriction fragment length polymorphism analysis using a modified primer pair and the restriction endonuclease HindIII. The osteocalcin genotype was determined in 160 postmenopausal Japanese women (age 48-80 years). Osteocalcin alleles were designated according to the absence (H) or presence (h) of the HindIII restriction site. There were 12 HH, 49 Hh, and 99 hh individuals, and the allele frequencies were 22.8% for H and 77.2% for h. To determine if genetic variation influences bone mineral density (BMD) and thus can be a determinant of susceptibility to osteoporosis in older women, we examined the association of BMD with the osteocalcin genotypes found in the present study. The subjects with genotype HH had the smallest BMD and those with hh had the greatest BMD among subjects, but these differences did not reach statistical significance. The HindIII genotype showed a significant effect on the prevalence of osteopenia in the subjects, that is, women with genotype HH had a 5.74 times greater risk for osteopenia (p < 0.05) and those with genotype Hh had a 1.59 times greater risk than women with genotype hh. We identified the osteocalcin gene polymorphism, detected with the HindIII genotype, which was suggested to influence bone density and is a possible genetic marker for bone metabolism.

Relative contributions of age and menopause to the vertebral bone density of healthy Japanese women.

The relative contributions of age and menopause to vertebral bone mineral density were evaluated based on the estimated weights for age- and menopause-related bone loss components using a mathematical model in 177 healthy female volunteers ages 35-81 years, living in a community in Fukui, Japan. Bone mineral density was determined by dual X-ray absorptiometry. The model used was that which afforded the best fit among the eight possible models to the data observed. Each model was composed of a linear function for the age-related component and a different type of function for the menopausal component, without interaction between them. The weights for these components in each model were estimated by the least-squares method. The coefficient of determination and Akaike information criterion disclosed that among the eight models tested, the model affording the best fit was composed of a logarithmic decrease in bone density with an increase in years since menopause, up to 10 years postmenopausal, with no further decline thereafter. In this model, the weights for both components were statistically significant and the type III sum of squares of the menopausal component was greater than that of the age-related component. We suggest that both age and menopause made significant contributions to the decline in vertebral bone mineral density, with the contribution of menopause being greater than that of age.

Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women.

The change in lumbar vertebral bone mineral density (BMD) during a 2-year study period was examined in 167 healthy middle-aged and elderly Japanese women with reference to age, menopausal status and bone turnover markers at baseline. The perimenopausal and postmenopausal groups of the subjects showed a significant loss of BMD during the study period but the premenopausal women did not. The annual percent decrease of BMD (delta BMD) in the perimenopausal women (-2.40% in average) was significantly greater than that in either of the premenopausal (-0.01%) or over-all postmenopausal women (-0.85%). The subjects who had been postmenopausal for less than 10 years showed a significant bone loss. delta BMD in the postmenopausal women became less marked as the postmenopausal duration increased. The bone loss was accelerated for about 10 years after menopause. The pattern and magnitude of bone loss of Japanese women seemed to be similar to those of Caucasian women. The regression equation for delta BMD based on the bone turnover markers at baseline was shown to be significant in the postmenopausal women and the serum level of bone-specific alkaline phosphatase isoenzyme had a significant relation to delta BMD. However, this equation accounted for only 17.3% of the total variance of delta BMD and, hence, its validity was not sufficiently high for the prediction of bone loss in clinical settings.

Maternal program of apoptosis activated shortly after midblastula transition by overexpression of S-adenosylmethionine decarboxylase in Xenopus early embryos.

When we studied polyamine metabolism in Xenopus embryos, we cloned the cDNA for Xenopus S-adenosylmethionine decarboxylase (SAMDC), which converts SAM (S-adenosylmethionine), the methyl donor, into decarboxylated SAM (dcSAM), the aminopropyl donor, and microinjected its in vitro transcribed mRNA into Xenopus fertilized eggs. We found here that the mRNA injection induces a SAM deficient state in early embryos due to over-function of the overexpressed SAMDC, which in turn induces inhibition of protein synthesis. Such embryos developed quite normally until blastula stage, but stopped development at the early gastrula stage, due to induction of massive cell dissociation and cell autolysis, irrespective of the dosage and stage of the mRNA injection. We found that the dissociated cells were TUNEL-positive, contained fragmented nuclei with ladder-forming DNA, and furthermore, rescued completely by coinjection of Bcl-2 mRNA. Thus, overexpression of SAMDC in Xenopus embryos appeared to switch on apoptotic program, probably via inhibition of protein synthesis. Here, we briefly review our results together with those reported from other laboratories. After discussing the general importance of this newly discovered apoptotic program, we propose that the maternal program of apoptosis serves as a surveillance mechanism to eliminate metabolically severely-damaged cells and functions as a 'fail-safe' mechanism for normal development in Xenopus embryos.

[Bone mineral density of lumbar spine and its relations to biological and lifestyle factors in middle-aged and aged Japanese women (Part 2). Effects of age and menopause on bone mineral density evaluated by biochemical markers of bone metabolism].

Bone mineral density of the lumbar spine (BMD) and biochemical markers for bone turnover were examined to study the mechanisms of age-related and menopause-related bone loss. We measured BMD of the lumbar spine and serum bone alkaline phosphatase (B-AIP) and bone gla-protein (BGP) as markers of bone formation and fasting urinary creatinine-adjusted hydroxyproline (Hyp/Cr) and calcium (Ca/Cr) as those of bone resorption in 166 community-dwelling Japanese women. A highly significant positive correlation between age and each of the biochemical markers, except for Ca/Cr, was observed. This relationship was not linear. Marked elevation in the levels of the markers was found in women in their sixth decade women compared with those in their fifth. All the markers correlated inversely with the BMD and these relationships remained significant after elimination of the effect of age by partialization. When analyzing the subjects in each five-year age group, the positive correlation of Hyp/Cr with Ca/Cr was significant in the subjects aged 45 to 49 and the negative correlation of Hyp/Cr with BMD was significant in those aged 50 to 54. B-AIP correlated positively with BGP in the subjects aged between 50 and 54 and inversely with BMD in those aged between 55 and 59. These correlations were significant. Thus, intercorrelations between the markers were observed five years earlier than were correlations between the markers and BMD. Such associations appeared earlier in terms of the markers for bone resorption than in terms of the markers for bone formation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cumulative incidence rate of divorces for birth cohort estimated by the life-table method].

The trend of divorces has been usually evaluated by the divorce rate. However, it is difficult to make detailed analyses of the trend of or relevant factors concerning divorces by the divorce rate, because the denominator of this index is not a population at risk of divorces. The application of the life-table method to calculation of cumulative incidence rate of divorces for a birth cohort based on vital statistics data was introduced and its problems were discussed. This method was able to give a precise incidence rate of divorces and made it possible to examine the relationship of marital durations, generation of cohorts or age at marriage to the incidence of divorces. The results obtained were as follows: 1. The cumulative incidence rate of divorces increased and the marital duration-specific incidence rate of divorces decreased with continuation of marriages. 2. The cumulative incidence rate of divorces was higher in younger birth cohorts than in older cohorts. 3. The cumulative incidence rate of divorces was the lowest in the cohort married when the husband was 23 to 32 years of age than in the cohorts with other ages at marriage in all the birth cohorts examined.

[Rate of incidence of divorce in birth cohorts classified by age difference between married couples].

We examined the situation concerning divorce in Japan from the view-point of age difference between married couples using vital statistics from the year 1952 to 1985. Annual and cumulative divorce rates were introduced as rate of incidence of divorce. We studied these indices by age difference between couples in birth cohorts of husbands. Our conclusions were as follows: 1) The cumulative divorce rate was lower in early birth cohorts than in late birth cohorts. 2) The cumulative divorce rate for young adult couples (aged 20-30) was higher than that for middle-aged couples (aged more than 30) in every cohort. 3) The cumulative divorce rate was lowest when husbands were 1 to 4 years older than wives. This tendency was quite similar in different ages and cohorts. 4) The same conclusions were reached when the annual divorce rate was substituted for the cumulative divorce rate.

[Bone mineral density of the lumbar spine and its relation to biological and lifestyle factors in middle-aged and aged Japanese women (Part 3). Relationships of physical fitness and lifestyle factors to bone mineral density in premenopausal and postmenopausal women].

We recruited community-dwelling women for participation in a study to investigate the effects of risk factors in lifestyle on bone mineral density (BMD). The subjects were 177 women aged 35 years and over living in a rural area in Fukui Prefecture. Their BMD of the lumbar spine (L2-L4) was determined by dual energy X-ray absorptiometry (DXA). In addition to measurements of height, body weight and grip strength, the lifestyles of the women, including physical load in work, sporting activities, smoking habits, calcium intake, and history of bone fracture were interviewed in detail. Adjusted for age, the BMD significantly correlated to body weight (r = 0.337, p < 0.05 for premenopausal women and r = 0.289, p < 0.01 for postmenopausal women) and body mass index (kg/m2) (r = 0.291, p < 0.05 for premenopausal women and r = 0.190, p < 0.05 for postmenopausal women). These results indicated the lower body weight to be a risk factor for the osteoporotic process in middle-aged and aged women. With respect to the grip strength as a physical fitness indicator, a significant correlation coefficient (r = 0.267, p < 0.01) with BMD was obtained for postmenopausal women independent of age and body weight. In univariate analysis, BMD showed no significant correlations with sporting activities, smoking habits, lower back pain and history of bone fracture for either premenopausal women or postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bone mineral density of the lumbar spine and its relation to biological and lifestyle factors in middle-aged and aged Japanese women (Part 1). Relationship of age and menopause to bone mineral density of the lumbar spine measured by dual-energy X-ray absorptiometry].

Bone mineral density (BMD) of the lumbar spine in 198 community-dwelling Japanese women aged 35 years and over was measured by dual-energy X-ray absorptiometry to investigate the effects of aging and menopause on BMD. A highly significant negative correlation between age and BMD was observed in postmenopausal women as widely accepted. We found a weak but statistically significant negative correlation between age and BMD in even premenopausal women, suggesting that their bone loss had commenced before menopause. Marked decrement in BMD was seen during the first ten years after menopause. Menopause clearly accelerated bone loss in the lumbar spine. Two-way analysis of variance of BMD on age and menopausal status showed that these explanatory variables had a significantly decreasing effect on BMD independently of each other. Menopausal status had a greater sum of squares than age, which suggested that menopause played a greater role in bone loss than did aging. Early menopause has been implied as one of the risk factors for bone loss. The women aged 50 to 59 having encountered menopause before 49 years old exhibited significantly lower BMD than those of similar age who experienced menopause at age 49 and older. This difference in BMD was not observed in the women aged 60 and over. Early menopause was no more likely to be a risk factor for bone loss in the elderly women. We conclude that bone loss in the lumbar spine begins before menopause and is accelerated markedly by menopause for about ten years, and that menopause has a greater decreasing effect on the bone mass than does chronological age while each of them has an independent effect on the bone mass decrement.